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Biomedical subjects

N Wong

Publications and source records attributed to N Wong.

At least 55 records · Page 3Linked to original sources

Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: relationship to disease stage, tumor size, and cirrhosis.

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prevalent in Southeast Asia. Although the etiological factors associated are now well recognized, the interactions between individual factors and the molecular mechanisms by which they lead to cancer remain unclear. Cytogenetic analysis on HCC has been limited because of poor hepatocyte growth in vitro. The recently developed technique of comparative genomic hybridization (CGH), however, permits screening of the entire genome without the need of cell culture. CGH was applied to the study of genomic aberrations in 67 surgically resected samples of HCC, 3 of adenomatous hyperplasia (AH), and 12 of nontumorous cirrhotic liver surrounding the tumors. All samples were from patients of a racially and etiologically homogeneous population in Southern China, where chronic hepatitis B virus infection is the main etiological factor. CGH analysis of the HCC samples revealed frequent copy number gain of 1q (48/67 cases, 72%), 8q (32/67 cases, 48%), 17q (20/67 cases, 30%), and 20q (25/67 cases, 37%) and common losses on 4q (29/67 cases, 43%), 8p (25/67 cases, 37%), 13q (25/67 cases, 37%), and 16q (20/67 cases, 30%). Our finding of a high incidence of 1q gain strongly suggested this aberration was associated with the development of HCC. Genomic abnormalities were detected in 1 of the 3 AH specimens but absent in all 12 cirrhotic tissues surrounding the tumor. Clinical staging classified 3/67 HCC cases as T1, 53 cases as T2, and 11 cases as T3. No significant difference in the pattern of genomic imbalances was detected between stages T2 and T3. A significant copy number loss of 4q11-q23 was, however, identified in those tumors larger than 3 cm in diameter. Of particular interest was the identification of 8q copy number gain in all 12 cases of HCC that arose in a noncirrhotic liver, compared with only 20/55 cases in HCC arising in a cirrhotic liver. We suggest that 8q over-representation is likely associated with a growth advantage and proliferative stimulation that have encouraged malignant changes in the noncirrhotic human liver.

Adult↗

The effect of the I1307K APC polymorphism on the clinicopathological features and natural history of breast cancer.

The I1307K polymorphism in APC has been found to predispose to colorectal cancer in Ashkenazi Jews, and has recently been associated with an increased risk for breast cancer in the same population. In that study, we genotyped 205 paraffin-embedded breast cancers from Ashkenazi Jewish women diagnosed below the age of 65. We now present an extended analysis, with clinicopathological correlations between carriers of I1307K and non-carriers. Twenty-four of 209 cases (11.5%, 95% confidence interval 7.5-16.6) were found to carry the I1307K polymorphism. When stratifying the data by other relevant clinicopathological variables, we observed no association between the presence of this polymorphism and age at diagnosis (P = 0.52), grade (P = 0.074), tumour size (P = 0.99), lymph node status (P = 0.82), oestrogen receptor status (P = 0.23) or P53 immunoreactivity (P = 0.80). The breast-cancer specific 5-year survival for women with I1307 K polymorphism was 88.9% compared with 81.6% in women without I1307K (P = 0.34). Using microdissected samples and direct sequencing, no somatic mutations were observed in any of the 24 I1307K-positive cases. Single-strand conformation analysis of 158 of the I1307K-negative breast cancers that were available for study revealed no mobility shifts. We conclude that the presence of the I1307K polymorphism does not appear to be associated with any particular clinicopathological feature of breast cancer and importantly, does not affect the prognosis.

Adenomatous Polyposis Coli Protein↗

Detection of chromosome over- and underrepresentations in hyperdiploid acute lymphoblastic leukemia by comparative genomic hybridization.

Chromosomal analysis of acute lymphoblastic leukemia (ALL) is often difficult because of the suboptimal in vitro growth of the immature lymphoid cell and the poor morphology obtained. In this study, we describe the application of comparative genomic hybridization (CGH) to investigate the genomic abnormalities in 14 patients with ALL, all of whom had cytogenetically identified numerical aberrations or gross chromosomal structural alteration. With the use of CGH, regional or whole chromosome overrepresentation or both were found to be more frequent than underrepresentation (52 gains vs. 6 losses), the most common gains being chromosomes 21 and X. The results of the comparison between CGH and conventional R-banding analysis could be classified into three categories: (1) in three cases, including two with trisomy, CGH and banding analysis gave identical results; (2) in six cases with hyperdiploidy and two cases presenting chromosome structural abnormalities, the results were consistent but with minor discrepancies; (3) in three cases, including two with triploidy and tetraploidy and one with chimeric karyotype together with +22, the data from CGH and cytogenetical analysis were discrepant. CGH could not find the triploidy and tetraploidy. Our results suggest that CGH has certain value in the detection of gains or losses of chromosome materials in hyperdiploid ALL. Nevertheless, the combination of CGH and conventional karyotyping provides more precise information on the genomic imbalance in ALL.

Adolescent↗

Statewide assessment of school-age children with asthma in Delaware.

In Delaware, asthma affects almost 14,000 children. The American Lung Association of Delaware and the University of Delaware surveyed school nurses to identify the needs of children with asthma and the services and accommodations available for these children. Researchers developed a survey instrument that was mailed to all Delaware schools (N = 324). The response rate was 38.6% (n = 125). According to respondents, a variety of protocols were in place regarding the administration of asthma medications. Respondents also reported that several measures had been taken to modify the school environment to improve air quality and reduce asthma triggers. Most respondents (77%) indicated they did not have asthma education programs in their schools. Findings from this study sparked development of a multidisciplinary Delaware Asthma Committee, an Asthma Education Center, and a statewide system for communicating with the parents of children with asthma.

Adolescent↗

Consistent copy number gain in chromosome 12 in primary diffuse large cell lymphomas of the stomach.

Fifteen cases of high grade primary gastric non-Hodgkin's lymphomas were studied using comparative genomic hybridization (CGH) and/or fluorescence in situ hybridization (FISH) techniques. A total of 10 cases of diffuse large cell lymphoma (DLCL) with no histologically identifiable or previous history of low grade mucosa-associated lymphoid tissue (MALT) lymphoma components were examined, four by CGH and validated by FISH, and the remaining six by FISH alone. All 10 tumors showed gains in chromosome 12. Other recurring CGH findings in DLCL included copy number gains of 1q and deletions of 6q. Five cases of high grade tumors with low grade MALT components (HGM) were also examined, three by CGH and validated by FISH and two by FISH only. Only one in five HGM showed gains of chromosome 12. Other recurring CGH findings in HGM included +7q and +11q. We conclude that high grade gastric lymphomas of DLCL type were associated with gains in chromosome 12. The change was much less frequent (P < 0.01) in the HGM type, which had a percentage similar to that observed in previously reported cytogenetics/FISH studies on low grade MALT lymphomas. Our findings suggested that many DLCL were not derived from transformation of low grade MALT lymphomas.

Adult↗

Electron beam computed tomographic coronary calcium as a predictor of coronary events: comparison of two protocols.

BACKGROUND: We assessed the accuracy of two electron beam computed tomography (EBCT) protocols for predicting coronary events. METHODS AND RESULTS: In 1994, 24 months after enrollment in a longitudinal study, 326 high-risk adults underwent both 3- and 6-mm image-slice thickness EBCT scanning and were followed up for 32.0+/-4.0 additional months. Events were defined as either coronary death, myocardial infarction, or revascularization. We monitored these subjects for the 32-month postscanning period with yearly phone calls and acquisition of records for all hospital admissions. At the time of scanning, 11 subjects (3%) had already suffered 12 events (5 infarctions and 7 revascularizations) during the 24-month prescanning period. During the postscanning period, 18 subjects (6%) suffered 23 events (5 coronary deaths, 6 infarctions, and 12 revascularizations). Thus, 28 subjects (9%) suffered 35 events. Calcium quantities calculated for both protocols, performed on the same subjects, were sorted in ascending order and divided into equal quartiles. When revascularizations were included, there was a significant trend toward higher frequencies of events with increasing calcium quantity (P<.01). However, coronary death and infarction were not significantly more frequent in higher quartiles. These relationships were preserved in the subjects without prior events at the time of scanning. CONCLUSIONS: Calcium quantities from the 3-mm and the more reproducible 6-mm scanning are equally accurate for predicting events. Coronary calcium amount appears to be a weak predictor of coronary death and infarction. Its predictive accuracy is superior for predicting revascularization.

Aged↗

Carbamazepine-induced lymphadenopathy mimicking Ki-1 (CD30+) T-cell lymphoma.

A 22 year old male receiving carbamazepine for a bipolar affective disorder presented with pyrexia, generalized rash, lymphadenopathy and hepatosplenomegaly. He was thrombocytopenic and liver function tests revealed a hepatitic picture. Lymph node histology suggested a T-cell lymphoma with many large cells possessing blastic features, and expressing CD3 and CD30 antigens. The abnormalities resolved completely within nine weeks of discontinuing carbamazepine, indicating that the presenting lymphadenopathy was secondary to lymphoid activation, ie; a pseudolymphoma rather than a malignant lymphoma. This is the first reported case of carbamazepine-induced lymphadenopathy with CD30+ cells. It illustrates the potential danger of relying too heavily on CD30 positivity as an indicator of malignancy.

Adult↗

Germ-line BRCA1 mutation is an adverse prognostic factor in Ashkenazi Jewish women with breast cancer.

Germ-line mutations in BRCA1 confer an increased risk of developing breast and ovarian cancer, but little is known about the clinical course of breast cancer in BRCA1 mutation carriers compared with noncarriers. Two recurrent BRCA1 mutations (185delAG and 5382insC) are common ( approximately 1.3%) in Ashkenazi Jews and account for about 20% of breast cancers diagnosed before age 40 in this group. We assayed paraffin-embedded tumor blocks from 117 unselected Ashkenazi Jewish women with primary breast cancer, diagnosed before age 65 at a single institution, for the presence of either of the two BRCA1 mutations. We reviewed the medical records and constructed survival curves for BRCA1-positive and -negative subgroups. Twelve of the women (10.3%) were found to carry BRCA1 mutations (eight mutations were 185delAG, and four were 5382insC). The probability of death from breast cancer in the first 5 years was 35.7% in the BRCA1 mutation-positive group and 4.3% in the 100 women without a mutation (P = 0.0023). The 5-year distant disease-free survival was 68.2% in BRCA1 mutation carriers and 88.7% in noncarriers (P = 0.019). These data suggest that breast cancer occurring in an Ashkenazi Jewish woman carrying a germ-line BRCA1 mutation has an adverse prognosis. This information is available before the diagnosis of breast cancer, and therefore, this finding may have important implications for prevention of breast cancer in BRCA1 mutation carriers.

Breast Neoplasms↗

Detection of coronary calcification with electron-beam computed tomography: evaluation of interexamination reproducibility and comparison of three image-acquisition protocols.

The purpose of this investigation was to determine the variability of electron-beam computed tomography (EBCT) measurement of coronary calcification by using two commonly employed image-acquisition protocols and to compare this variability with that of a new image-acquisition protocol. We performed three EBCT scans within 15 minutes on each of 324 consecutive high-risk, asymptomatic subjects participating in an ongoing epidemiologic research investigation. Subjects were divided into three groups: group 1 (n = 175) received two scans with a standard 20-slice, 3 mm slice thickness image-acquisition protocol and a third scan with the new 20-slice, 6 mm slice thickness protocol; group 2 (n = 77) received two scans with a new 6 mm slice thickness image-acquisition protocol and a third scan with a standard 20-slice, 3 mm slice thickness protocol; group 3 (n = 72) received two scans with a 30-slice, 3 mm slice thickness image-acquisition protocol and a third scan with a 20-slice, 6 mm slice thickness protocol. Calcium score, calcium mass estimate, and calcium volume estimate were determined for each scan. We compared retest variability of calcium measurements for each of the three image-acquisition protocols. The variability of the new 6 mm slice thickness protocol was significantly lower than that of either the 20-slice 3 mm slice thickness protocol (p = 0.009) or the 30-slice 3 mm slice thickness protocol (p = 0.02) for measurement of calcium score, mass, or volume. Retest reproducibility for all three image-acquisition protocols was low; however, the 20-slice 6 mm slice thickness protocol gave reproducibility superior to either of the 3 mm slice thickness protocols. Variability of absolute indices increased, and variability of relative indices decreased as the value of these indices increased. EBCT is not sufficiently reproducible to allow serial quantitation of coronary calcium in individual patients over relatively short periods (< 2 years).

Aged↗

Small cell variant of Ki-1 lymphoma associated with myelofibrosis and a novel constitutional chromosomal translocation t(3;4) (q13;q12).

An unusual case of small cell variant of Ki-1 non-Hodgkin's lymphoma diagnosed one year after an original diagnosis of idiopathic myelofibrosis is reported. On the second occasion, the patient presented with fever, lymphadenopathy and hepatosplenomegaly. A lymph node biopsy specimen confirmed a diagnosis of small cell variant of Ki-1 lymphoma. A repeat bone marrow biopsy specimen showed myelofibrosis with no evidence of lymphomatous infiltration, but cytogenetic studies on blood, bone marrow and skin fibroblasts revealed a novel chromosomal translocation t(3,4)(q13;q12).

Chromosome Mapping↗

An improved method for the quantitation of apolipoprotein B and apolipoprotein A-1 in dried blood spots.

An extraction protocol has been developed to elute apolipoprotein B (apo B) and apolipoprotein A-1 (apo A-1) from dried blood spots with assay of the extracted apolipoproteins by automated immunoturbidimetry. Various extraction media were investigated to assess their elution efficiency and the optimum medium was found to be deionized water. Studies on the rate of elution suggested both apolipoproteins were eluted readily in less than an hour with a recovery of 71% for apo B and 65% for apo A-1. Extracted apo B but not aop A-1 was found to be stable for 24 h when kept at 4 degrees C. The within-batch coefficients of variation (CV) for the combined extraction and assay of apo B were found to be 5.9% and 8.5% at 0.6 g/L and 1.2 g/L respectively. The CVs for apo A-1 were found to be 7.4% at 0.7 g/L and 8.9% at 1.5 g/L. Antiserum from three sources (Immuno, Incstar and Bayer) was investigated for immunoreactivity with apo B and apo A-1 and cross-reactivity with red blood cells was also assessed. Although the antisera from the three companies showed similar immunoreactivity towards apo B and apo A-1, antiserum from Bayer was found to cross-react with red cells.

Adult↗